SGLT-2 Inhibitor Empagliflozin Effects on Appetite and Weight Regulation.

NCT02798744 | Completed Phase 4 DMC

• 1 other identifier: 0526
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to investigate the cause for the discrepancy in predicted and observed weight loss with Empagliflozin (Jardiance™) by measuring appetite regulation. Major secondary objectives are to determine the effects of Empagliflozin (Jardiance™) on energy expenditure and change in total body weight and body composition. The primary outcome is change in appetite hormone concentrations (specifically total PYY) between baseline and 24 weeks: - this will be measured by sequential blood sampling during visits 1-5. Secondary outcomes, which are exploratory, are effect on appetite hormones (ghrelin and GLP-1), appetite perceptions, total body weight and fat and fat free mass, energy expenditure, appetite perception, physical activity and blood and urine biochemical parameters after Empagliflozin (Jardiance™) treatment for 24 weeks. The sample size for the study is 76 participants and the planned trial duration is 21 months, with participants receiving approximately 24 weeks of exposure to Empagliflozin (Jardiance™).

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• Change from baseline in Total PYY at 24 weeks

  The effect of Empagliflozin on appetite hormone 'Total PYY' concentration between baseline and 24 weeks. Measured by sequential blood sampling at study visits 1-5.

  Baseline and 24 weeks

Secondary Outcomes (14)

• Change from baseline in Ghrelin at 24 weeks

  Baseline and 24 weeks

• Change from baseline in GLP-1 to 24 weeks

  Baseline and 24 weeks

• Change from baseline in appetite perceptions to 24 weeks

  Baseline and 24 weeks

• Change in Weight (kg) from baseline to 24 weeks

  Baseline and 24 weeks

• Change in Body composition from baseline to 24 weeks

  Baseline and 24 weeks

Study Arms (4)

Empagliflozin 25mg once daily

EXPERIMENTAL

Empagliflozin (Jardiance™) 25mg once daily (orally)

Drug: Empagliflozin

Empagliflozin 25mg once daily + diet

EXPERIMENTAL

Empagliflozin (Jardiance™) 25mg once daily (orally) + energy restriction diet

Drug: Empagliflozin; Behavioral: Diet

Placebo once daily

PLACEBO COMPARATOR

Placebo once daily (orally)

Drug: Placebo

Placebo once daily + diet

ACTIVE COMPARATOR

Placebo once daily (orally) + energy restriction diet

Behavioral: Diet; Drug: Placebo

Interventions

Empagliflozin DRUG

25mg once daily to be taken orally for the duration of the study (24 weeks)

Also known as: Jardiance

Empagliflozin 25mg once daily; Empagliflozin 25mg once daily + diet

Diet BEHAVIORAL

Daily energy restriction diet to be followed for the duration of the study (24 weeks)

Also known as: Energy restriction diet

Empagliflozin 25mg once daily + diet; Placebo once daily + diet

Placebo DRUG

Placebo once daily for the duration of the study (24 weeks)

Placebo once daily; Placebo once daily + diet

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and postmenopausal female participants aged between 30-75 years of age inclusive
• Type 2 diabetes on diet and lifestyle control or stable dose of metformin only for at least 3 months
• Stable weight (less than 5% change in body weight in last 3 months) - determined by self-reporting or documentation in clinical records
• HbA1c 48-86mmol/mol (6.0 - 10%)
• eGFR≥60ml/min/1.73m2
• BMI ≥ 25kg/m2
• Able and willing to give informed consent
• Able to understand English

You may not qualify if:

• Females who are not postmenopausal (as menstrual cycle can affect appetite hormone concentrations) which is defined as "2 years post last menstrual period \<50 years of age or 1 year post last menstrual period \>50 years of age."
• Type 2 diabetes on any other glucose lowering treatment except metformin
• Patients with Type 1 diabetes
• Patients on loop diuretics
• Age \<30 years and \>75 years
• BMI \<25kg/m2
• Not able to give informed consent
• Not able to understand English
• Moderate to severe renal impairment (eGFR\<60ml/min/1.73m2)
• Unstable diabetes i.e. HbA1c \>86mmol/mol (10%), recent hospital admission with diabetic emergency in last 3 months
• Patients with familial renal glycosuria
• Patients with recurrent balanitis, vaginal or urinary tract infections
• Shift workers
• Patients who have participated in another study of an investigational medicinal product in the last 3 months
• Active malignancy

Sponsors & Collaborators

• University of Leicester: lead
• Loughborough University: collaborator
• University Hospitals, Leicester: collaborator

Study Sites (1)

Leicester Diabetes Centre

Leicester, LE5 4PW, United Kingdom

Location

Related Publications (22)

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• Ferrannini E, Seman L, Seewaldt-Becker E, Hantel S, Pinnetti S, Woerle HJ. A Phase IIb, randomized, placebo-controlled study of the SGLT2 inhibitor empagliflozin in patients with type 2 diabetes. Diabetes Obes Metab. 2013 Aug;15(8):721-8. doi: 10.1111/dom.12081. Epub 2013 Mar 4.

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• Ferrannini G, Hach T, Crowe S, Sanghvi A, Hall KD, Ferrannini E. Energy Balance After Sodium-Glucose Cotransporter 2 Inhibition. Diabetes Care. 2015 Sep;38(9):1730-5. doi: 10.2337/dc15-0355. Epub 2015 Jul 15.

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• Haring HU, Merker L, Seewaldt-Becker E, Weimer M, Meinicke T, Broedl UC, Woerle HJ; EMPA-REG MET Trial Investigators. Empagliflozin as add-on to metformin in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial. Diabetes Care. 2014 Jun;37(6):1650-9. doi: 10.2337/dc13-2105. Epub 2014 Apr 10.

  PMID: 24722494 BACKGROUND

• Kovacs CS, Seshiah V, Swallow R, Jones R, Rattunde H, Woerle HJ, Broedl UC; EMPA-REG PIO trial investigators. Empagliflozin improves glycaemic and weight control as add-on therapy to pioglitazone or pioglitazone plus metformin in patients with type 2 diabetes: a 24-week, randomized, placebo-controlled trial. Diabetes Obes Metab. 2014 Feb;16(2):147-58. doi: 10.1111/dom.12188. Epub 2013 Aug 22.

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• Ridderstrale M, Andersen KR, Zeller C, Kim G, Woerle HJ, Broedl UC; EMPA-REG H2H-SU trial investigators. Comparison of empagliflozin and glimepiride as add-on to metformin in patients with type 2 diabetes: a 104-week randomised, active-controlled, double-blind, phase 3 trial. Lancet Diabetes Endocrinol. 2014 Sep;2(9):691-700. doi: 10.1016/S2213-8587(14)70120-2. Epub 2014 Jun 16.

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• Sargeant JA, King JA, Yates T, Redman EL, Bodicoat DH, Chatterjee S, Edwardson CL, Gray LJ, Poulin B, Waheed G, Waller HL, Webb DR, Willis SA, Wilding JPH, Khunti K, Stensel DJ, Davies MJ. The effects of empagliflozin, dietary energy restriction, or both on appetite-regulatory gut peptides in individuals with type 2 diabetes and overweight or obesity: The SEESAW randomized, double-blind, placebo-controlled trial. Diabetes Obes Metab. 2022 Aug;24(8):1509-1521. doi: 10.1111/dom.14721. Epub 2022 May 13.

  PMID: 35441435 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

empagliflozin; Diet

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Melanie J Davies, MBBS MD FRCP

  University of Leicester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2016
• First Posted: June 14, 2016
• Study Start: December 1, 2016
• Primary Completion: July 30, 2019
• Study Completion: July 30, 2019
• Last Updated: January 30, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)